csm5 Resolved · high auto-curated
H37Rv Rv2819c · MTBC0 mtbc0_002997 ·
375 aa · 3146897–3148024 (-) ·
RefSeq NP_217335.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CRISPR type III-associated RAMP protein Csm5 |
|---|---|
| MTBC0 PGAP re-annotation | type III-A CRISPR-associated RAMP protein Csm5 |
| Revised (this work) | Type III-A CRISPR-associated RAMP protein Csm5. Pfam: RAMPs (PF03787.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJF5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRISPR system Cms protein Csm5 |
| Curated function | CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activiti. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | csm5 |
| eggNOG description | CRISPR-associated RAMP protein, Csm5 family |
| Orthologous group | COG1332 |
| KEGG orthology |
K19140
|
| Gene Ontology (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 1.281 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.25% of strains (361) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
RAMPs | PF03787.21 | 4.3e-09 | 11–270 | RAMP superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: csm4 (CRISPR type III-associated RAMP protein Csm4), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2820c csm4 |
CRISPR type III-associated RAMP protein Csm4 | 999 | 1000 ctx | neighborhood:801 fusion:448 cooccurence:774 coexpression:847 experimental:911 textmining:857 |
Rv2821c csm3 |
CRISPR type III-associated RAMP protein Csm3 | 999 | 999 ctx | neighborhood:801 cooccurence:728 coexpression:804 experimental:927 textmining:887 |
Rv2822c csm2 |
CRISPR type III-associated protein Csm2 | 999 | 999 ctx | neighborhood:801 cooccurence:774 coexpression:806 experimental:927 textmining:852 |
Rv2823c cas10 |
CRISPR-associated protein Cas10/Csm1 | 999 | 997 ctx | neighborhood:801 cooccurence:772 experimental:919 textmining:830 |
Rv2824c cas6 |
CRISPR-associated endoribonuclease Cas6 | 990 | 953 ctx | neighborhood:793 cooccurence:774 textmining:803 |
Rv2818c csm6 |
CRISPR-associated protein Csm6 | 988 | 944 ctx | neighborhood:625 coexpression:857 textmining:803 |
Rv2816c cas2 |
CRISPR-associated endoribonuclease Cas2 | 920 | 851 ctx | neighborhood:559 cooccurence:675 textmining:489 |
Rv0355c PPE8 |
PPE family protein PPE8 | 776 | 776 ctx | cooccurence:773 |
Rv3350c PPE56 |
PPE family protein PPE56 | 782 | 774 ctx | cooccurence:773 |
Rv0304c PPE5 |
PPE family protein PPE5 | 782 | 774 ctx | cooccurence:771 |
Rv3347c PPE55 |
PPE family protein PPE55 | 782 | 774 ctx | cooccurence:773 |
Rv1004c |
membrane protein | 773 | 774 ctx | cooccurence:773 |
Rv1917c PPE34 |
PPE family protein PPE34 | 773 | 773 ctx | cooccurence:772 |
Rv3343c PPE54 |
PPE family protein PPE54 | 780 | 772 ctx | cooccurence:771 |
Rv2209 |
integral membrane protein | 772 | 772 ctx | cooccurence:772 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: CRISPR type III-associated RAMP protein Csm5
- MTBC0 PGAP product: type III-A CRISPR-associated RAMP protein Csm5
- Pfam (hmmscan --cut_ga): RAMPs PF03787.21 (E=4e-09)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217335.1)
- Domains: Pfam-A via hmmscan --cut_ga — RAMPs (PF03787.21)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG1332 - Curated reference: UniProt P9WJF5 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
122 functional partner(s); context anchor
csm4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002997|Rv2819c|csm5 MNTYLKPFELTLRCLGPVFIGSGEKRTSKEYHVEGDRVYFPDMELLYADIPAHKRKSFEAFVMNTDGAQATAPLKEWVEPNAVKLDPAKHRGYEVKIGSIEPRRASRGRGGRMTRKKLTLNEIHAFIKDPLGRPYVPGSTVKGMLRSIYLQSLVHKRTAQPVRVPGHQTREHRQYGERFERKELRKSGRPNTRPQDAVNDLFQAIRVTDSPALRTSDLLICQKMDMNVHGKPDGLPLFRECLAPGTSISHRVVVDTSPTARGGWREGERFLETLAETAASVNQARYAEYRAMYPGVNAIVGPIVYLGGGAGYRSKTFVTDQDDMAKVLDAQFGKVVKHVDKTRELRVSPLVLKRTKIDNICYEMGQCELSIRRAE